In utero irradiation of rats as a model of human cerebrocortical dysgenesis: a review

Certain developmental abnormalities of the cerebral cortex are closely associated with epilepsy in humans. Exposure of fetal rats to external γ-irradiation produces diffuse cortical dysplasia and neuronal heterotopia. These abnormalities are the result of radiation-induced cell death coupled with continued cortical development in an altered cellular environment. In vivo electroencephalography studies in these animals have revealed an increased propensity for electrographic seizures in the presence of the sedating agents, acepromazine and xylazine. In vitro neocortical slices containing dysplastic cortex demonstrate enhanced excitability, as compared to control neocortex, when inhibition that is mediated by the A-type γ-amino butyric acid receptor is blocked with bicuculline methiodide. In utero irradiation of rats produces structural changes that mimic some aspects of cerebral dysgenesis in humans and results in physiologic changes that increase the animals' propensity for seizures. Similarities and differences between the animal model and the human syndromes are discussed.